| ln Vitro |
Gal-dMor-Gem (0.1-100 μM; 48 hours) can effectively and selectively reduce the viability of senescent A549/Dox and A549/H2O2 cells, and its efficacy is better than that of non-senescent A549 cells; its senescent cell clearance index is 48.3 and 56.7, respectively, and its IC50 values are 1.58 μM and 1.40 μM, respectively[1]. Gal-dMor-Gem (esterase 100 U/mL, β-galactosidase 5 U/mL) releases active gemcitabine (Gem) faster than Gal-Gem and Gal-Mor-Gem under the activation of esterase and β-galactosidase, with a release rate of 79.9% after 3 hours and a cumulative release rate of 92.4% after 12 hours[1]. Gal-dMor-Gem (3–48 hours) eliminated senescent A549/Dox cells faster and more effectively than Gal-Gem, with cell viability decreasing to 20.9% after 36 hours of treatment [1]. Gal-dMor-Gem (100 μM; 36 hours) selectively induced apoptosis in senescent A549/Dox cells, but did not have this selectivity for non-senescent A549 cells [1].
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| ln Vivo |
Gal-dMor-Gem (0.2-1.0 mg/kg; intraperitoneal injection; once a week; for a total of 3 times) can effectively alleviate doxorubicin (Dox)-induced systemic aging in mice, and a dose of 1.0 mg/kg can restore most aging-related biomarkers to levels close to those of healthy controls [1].
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| Cell Assay |
Cell viability assay [1]
Cell Types: Non-senescent A549 cells, senescent A549/Dox cells, senescent A549/H2O2 cells Tested Concentrations: 0.1-100 μM Incubation Duration: 48 h Experimental Results: The cytotoxicity to senescent cells was higher than that to non-senescent cells. At a concentration of 0.1 μM, the viability of A549 cells decreased to 91.7%, the viability of A549/Dox cells decreased to 83.0%, and the viability of A549/H2O2 cells decreased to 80.6%. At a concentration of 100 μM, the survival rates of A549 cells, A549/Dox cells, and A549/H2O2 cells decreased to 57.1%, 17.8%, and 11.3%, respectively. The IC50 values for A549 cells, A549/Dox cells, and A549/H2O2 cells were 79.54 μM, 1.58 μM, and 1.40 μM, respectively. The senescent cell clearance indices were 48.3 (A549/Dox) and 56.7 (A549/H2O2), respectively. Apoptosis analysis [1] Cell Types: Non-senescent A549 cells, senescent A549/Dox cells Tested Concentrations: 100 μM Incubation Duration: 36 h Experimental Results: Apoptosis was induced in 10.1% of non-senescent A549 cells and 50.4% of senescent A549/Dox cells. Compared with Gal-Gem, the apoptosis rate of non-senescent A549 cells induced in this study was lower, while the apoptosis rate of senescent A549/Dox cells was higher (Gal-Gem induced apoptosis in 21.5% of non-senescent A549 cells and 32.0% of senescent A549/Dox cells, respectively). |
| Animal Protocol |
Animal/Disease Models:C57BL/6J mice (doxycycline-induced systemic aging model) [1]
Doses: 0.2 mg/kg; 0.5 mg/kg; 1.0 mg/kg Route of Administration: Intraperitoneal injection; once a week; for a total of 3 times Experimental Results: Compared with the untreated control group, the weight of the aging mice in the treatment group increased; compared with day 10, the weight of the 0.5 mg/kg group increased by 14.6% and the weight of the 1.0 mg/kg group increased by 17.8%. The liver (ALT, AST) and kidney (CREA, UREA) function indicators were improved in all dosage groups, and the repair effect of the 0.5 mg/kg dosage group was better than that of the reference compound. The proportion of SA-β-gal positive cells in lung tissue decreased from 62.4% to 44.2% at a dose of 0.2 mg/kg, to 16.9% at a dose of 0.5 mg/kg, and to 9.9% at a dose of 1.0 mg/kg (close to the healthy level of 6.0%). The proportion of LMNB1 positive cell nuclei in lung tissue increased from 43.9% to 57.6% at a dose of 0.2 mg/kg, to 74.9% at a dose of 0.5 mg/kg, and to 82.0% at a dose of 1.0 mg/kg (close to the healthy level of 86.0%). The relative fluorescence intensity of IL-6 in lung tissue decreased from 1450.5 to 1205.0 at a dose of 0.2 mg/kg, to 678.1 at a dose of 0.5 mg/kg, and to 450.0 at a dose of 1.0 mg/kg. The proportion of SA-β-gal positive cells in the liver decreased from 88.1% to 63.7% at a dose of 0.2 mg/kg, to 21.7% at a dose of 0.5 mg/kg, and to 13.2% at a dose of 1.0 mg/kg (close to healthy levels of 6.9%). The relative expression level of p21 in the liver decreased from 0.93 to 0.78 at a dose of 0.2 mg/kg, to 0.58 at a dose of 0.5 mg/kg, and to 0.50 at a dose of 1.0 mg/kg. The relative expression level of p53 in the liver decreased to 0.49 at a dose of 0.5 mg/kg and to 0.43 at a dose of 1.0 mg/kg (close to healthy levels of 0.38). At all doses, the proportion of SA-β-gal positive cells in the heart and kidneys decreased, the number of LMNB1 positive cell nuclei increased, and IL-6 levels decreased, with the 0.5 mg/kg dose showing better effects than the reference compound. These indicators were restored to near-healthy levels at a dose of 1.0 mg/kg. |
| References |
| Appearance |
Typically exists as solids at room temperature
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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